HBV Core Particles as a Carrier for B Cell/T Cell Epitopes

Abstract

In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to icosahedral virus-like particles (VLPs) as a basic class of non-infectious carriers of foreign immunological epitopes. The recombinant HBc particles were used to display immunodominant epitopes of hepatitis B, C, and E virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and poliovirus, and other virus proteins, as well as of some bacterial and protozoan protein epitopes. Practical applicability of the HBc particles as carriers was enabled by their ability to high level synthesis and correct self-assembly in heterologous expression systems. The interest in the HBc VLPs was reinforced by the resolution of their fine structure by electron cryomicroscopy and X-ray crystallography, which revealed an unusual α-helical organization of dimeric units of HBc shells, alternative packing into icosahedrons with T = 3 and T = 4 symmetry, and the existence of long protruding spikes. The tips of the latter seem to be the optimal targets for the display of foreign sequences up to 238 amino acid residues in length. Combination of numerous experimental data on epitope display with the precise structural information enables a knowledge-based design of diagnostic, and vaccine and gene therapy tools on the basis of the HBc particles.

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

“…HBc fusion proteins often maintain the self-assembling ability and display inserted foreign epitopes on the tips of particle spikes if they are inserted into the MIR. 6 However, folding and capsid formations of the chimeric proteins are not always achieved easily, and the insert size and composition often are limitation factors in this process due to the conformational stress. Earlier it was shown that failure of some chimeric proteins to assemble into VLPs could be explained by the length of the insert; 120 amino acids are usually accepted as a maximum.…”

“…Dimer clustering of two HBc monomers produces spikes on the surface of the capsid, and the loop region located on top of these spikes (residues 78 -83) is the major target of the humoral response, i.e., major immunodominant region (MIR). 6,7 Generally HBc-based VLPs have been used as an epitope presentation system in vaccine design and antigen presentation studies. [8][9][10][11] On the other hand, the ability of HBc to incorporate peptides of different origin may be useful in the development of NPs for different application.…”

Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes

“…HBc⌬ vector carrying all HBc T-helper cell and cytotoxic-T-lymphocyte (CTL) epitopes but lacking the C-terminal arginine-rich region was chosen for epitope insertions as an efficient vaccine scaffold. The HBc MIR region and C terminus of such shortened HBcs were selected as the best places for insertions of HBV and HCV epitopes, respectively (30).…”

“…For this reason, the MIR is generally accepted as the target site of choice for insertion of foreign epitopes (30). The other widely accepted site for insertions is C-terminal position 144, a short stretch after the e2 epitope.…”

“…The other widely accepted site for insertions is C-terminal position 144, a short stretch after the e2 epitope. For C-terminal insertions, so-called HBc⌬ vectors lacking a 39-aa-long positively charged C-terminal histone-like fragment are preferred for their high insertion capacities (up to 741 amino acid residues) (30).…”